The role of gut derived endotoxin in the initiation and perpetuation of liver injury has been a major interest of this laboratory for 15 years. We have recently developed an immunoradiometric assay (IRMA) for a strain specific LPS (E. coli 026) that allows for the first time a gut marker to study the appearance and precise quantitation of enteric endotoxin after acute and chronic liver injury. Using the same methodology employed in the strain specific IRMA, progress is being made in developing a similar assay for lipid A which hopefully will allow quantitation of heterologous endotoxins. We are also studying the relationship of sinusoidal cells in the detoxification of LPS, and how liver injury alters this process. Using the IRMA assay to measure the clearance of E. coli 026, we have shown that acute and chronic alcohol administration markedly prolongs LPS clearance and CCl4 does so well, and as early as one hour after administration. Additionally we are studying the uptake and distribution of LPS by isolated Kupffer cells, endothelial cells and hepatocytes, from normal animals and from rats after graded liver injuries with CCl4 and galactosamine.